Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 55, Issue 7, Pages 3135-3143Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm2015952
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Funding
- National Science Fair Committee of China [NSFC 81102477]
- State Key Laboratory of Drug Research [SIMM1004KF-18]
- DENFRAME of the European Union (EC) [517711]
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The results of a high-throughput screening assay using the DENV-2 replicon showed that the 2,4-diaminoquinazoline derivative 4a has a high dengue virus inhibitory activity (EC50 = 0.15 mu M). A series of 2,4-diaminoquinazoline derivatives based on 4a as a lead compound were synthesized and subjected to structure-antidengue activity relationship studies. Among the series of 2,4-diaminoquinazoline derivative probed, 4o was observed to display both the highest antiviral potency (EC50 = 2.8 nM, SI > 1000) and an excellent pharmacokinetic profile.
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